Korzun Tetiana, Moses Abraham S, Diba Parham, Sattler Ariana L, Taratula Olena R, Sahay Gaurav, Taratula Oleh, Marks Daniel L
Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 S Moody Avenue, Portland, OR 97201, USA.
Department of Biomedical Engineering, Oregon Health & Science University, 3303 SW Bond Avenue, Portland, OR 97239, USA.
Pharmaceuticals (Basel). 2023 Jul 31;16(8):1088. doi: 10.3390/ph16081088.
In biomedical applications, nanomaterial-based delivery vehicles, such as lipid nanoparticles, have emerged as promising instruments for improving the solubility, stability, and encapsulation of various payloads. This article provides a formal review focusing on the reactogenicity of empty lipid nanoparticles used as delivery vehicles, specifically emphasizing their application in mRNA-based therapies. Reactogenicity refers to the adverse immune responses triggered by xenobiotics, including administered lipid nanoparticles, which can lead to undesirable therapeutic outcomes. The key components of lipid nanoparticles, which include ionizable lipids and PEG-lipids, have been identified as significant contributors to their reactogenicity. Therefore, understanding the relationship between lipid nanoparticles, their structural constituents, cytokine production, and resultant reactogenic outcomes is essential to ensure the safe and effective application of lipid nanoparticles in mRNA-based therapies. Although efforts have been made to minimize these adverse reactions, further research and standardization are imperative. By closely monitoring cytokine profiles and assessing reactogenic manifestations through preclinical and clinical studies, researchers can gain valuable insights into the reactogenic effects of lipid nanoparticles and develop strategies to mitigate undesirable reactions. This comprehensive review underscores the importance of investigating lipid nanoparticle reactogenicity and its implications for the development of mRNA-lipid nanoparticle therapeutics in various applications beyond vaccine development.
在生物医学应用中，基于纳米材料的递送载体，如脂质纳米颗粒，已成为改善各种有效载荷的溶解度、稳定性和封装的有前景的工具。本文提供了一篇正式综述，重点关注用作递送载体的空脂质纳米颗粒的反应原性，特别强调其在基于mRNA的疗法中的应用。反应原性是指由异生物素引发的不良免疫反应，包括所施用的脂质纳米颗粒，这可能导致不良的治疗结果。脂质纳米颗粒的关键成分，包括可电离脂质和聚乙二醇脂质，已被确定为其反应原性的重要促成因素。因此，了解脂质纳米颗粒、其结构成分、细胞因子产生和由此产生的反应原性结果之间的关系，对于确保脂质纳米颗粒在基于mRNA的疗法中的安全有效应用至关重要。尽管已经努力将这些不良反应降至最低，但进一步的研究和标准化势在必行。通过密切监测细胞因子谱，并通过临床前和临床研究评估反应原性表现，研究人员可以深入了解脂质纳米颗粒的反应原性效应，并制定减轻不良反应的策略。这篇全面的综述强调了研究脂质纳米颗粒反应原性及其对mRNA-脂质纳米颗粒疗法在疫苗开发以外的各种应用中的发展的影响的重要性。
